Most types of senile cataract are the result of aggregation and insolubilization of lens protein. The formation of soluble high molecular weight aggregates of lens crystallins has been studied extensively. However, the process by which the soluble aggregate becomes insoluble is not understood. The experiments outlined in this proposal use methods similar to those used in the study of fibrin clotting. The overall question is whether crystallins purified from calf lens can be induced in vitro to associate and form an insoluble gel in a manner analogous to fibrin clotting. This project will determine 1) factors necessary to induce aggregation; 2) time course required for aggregation; and 3) structure of the insoluble aggregate. Ultimately, of course, it will be desirable to determine factors which inhibit this aggregation process. Such factors could provide a pharmaceutical approach to the treatment of cataract.